Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Laboratory of Ultrastructural Virology, Graduate School of Biostudies, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Nat Commun. 2022 Mar 4;13(1):1191. doi: 10.1038/s41467-022-28802-x.
The nucleoprotein (NP) of Marburg virus (MARV), a close relative of Ebola virus (EBOV), encapsidates the single-stranded, negative-sense viral genomic RNA (vRNA) to form the helical NP-RNA complex. The NP-RNA complex constitutes the core structure for the assembly of the nucleocapsid that is responsible for viral RNA synthesis. Although appropriate interactions among NPs and RNA are required for the formation of nucleocapsid, the structural basis of the helical assembly remains largely elusive. Here, we show the structure of the MARV NP-RNA complex determined using cryo-electron microscopy at a resolution of 3.1 Å. The structures of the asymmetric unit, a complex of an NP and six RNA nucleotides, was very similar to that of EBOV, suggesting that both viruses share common mechanisms for the nucleocapsid formation. Structure-based mutational analysis of both MARV and EBOV NPs identified key residues for helical assembly and subsequent viral RNA synthesis. Importantly, most of the residues identified were conserved in both viruses. These findings provide a structural basis for understanding the nucleocapsid formation and contribute to the development of novel antivirals against MARV and EBOV.
马尔堡病毒（MARV）的核蛋白（NP）是埃博拉病毒（EBOV）的近亲，它将单链、负义病毒基因组 RNA（vRNA）包裹起来形成螺旋状的 NP-RNA 复合物。NP-RNA 复合物构成了核衣壳的核心结构，负责病毒 RNA 的合成。尽管 NP 与 RNA 之间的适当相互作用对于核衣壳的形成是必需的，但螺旋组装的结构基础在很大程度上仍难以捉摸。在这里，我们使用 cryo-electron microscopy 在 3.1 Å 的分辨率下确定了 MARV NP-RNA 复合物的结构。不对称单位的结构，即一个 NP 和六个 RNA 核苷酸的复合物，与 EBOV 非常相似，这表明这两种病毒在核衣壳形成方面具有共同的机制。基于结构的 MARV 和 EBOV NP 突变分析确定了螺旋组装和随后的病毒 RNA 合成的关键残基。重要的是，所鉴定的大多数残基在两种病毒中都保守。这些发现为理解核衣壳形成提供了结构基础，并有助于开发针对 MARV 和 EBOV 的新型抗病毒药物。
